Preparation method of rosuvastatin calcium intermediate

A technology for rosuvastatin calcium and intermediates, which is applied in the field of pharmaceutical synthesis, can solve the problems of increased synthesis steps and production costs, unsuitable for industrial production, harsh reaction conditions, etc., to avoid adverse effects, clean reaction, and mild reaction conditions Effect

Inactive Publication Date: 2017-10-10
SUZHOU HEALTH COLLEGE
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] (1) In the process of preparing compound 6 by oxidation of compound 5, a large amount of nitric acid is used as an oxidizing agent, which causes great environmental pollution, and post-treatment requires a large amount of lye to neutralize, resulting in low production efficiency;
[0011] (2) In the process of obtaining the target compound 1 by the reduction of compound 7, there are mainly two method...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of rosuvastatin calcium intermediate
  • Preparation method of rosuvastatin calcium intermediate
  • Preparation method of rosuvastatin calcium intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1.1 Preparation of formula II compound 5

[0035] Add methanol, 24.8g (0.2mol) of p-fluorobenzaldehyde, 28.8g (0.2mol) of methyl isobutyryl acetate, 21g (0.35mol) of urea, and 0.2g (0.002mol) of cuprous chloride into a 1000mL three-necked flask and 2mL of 1mol / L sulfuric acid, heated to 78°C for 9h, stirred at 0°C for 2h in an ice-water bath, filtered, washed 3 times with cold ethanol, and dried at 65°C to obtain 55.3g of compound 5, yield 94.5%, mp: 224~ 225°C. 1 H-NMR (CDCl 3 ,400MHz)δ:1.18~1.23(d,6H,CH 3 ×2),3.62(s,3H,CH 3 ), 4.13~4.16(m,1H,CHCH 3 CH 3 ),5.30(d,1H,CHNH),5.54(d,1H,CHNH), 6.86(s,1H,NH),6.99~7.02(m,2H,ArH),7.26~7.29(m,2H,ArH) .

[0036] 1.2 Synthesis of Formula III Compound 6

[0037] 55g (0.19mol) of compound 5, 50.8g (0.19mol) of potassium persulfate, 300ml of acetonitrile, and 60ml of water were added sequentially to a 500mL three-necked flask, heated to reflux, and stirred for 5h. After the reaction is complete, evaporate acetonitrile under...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a preparation method of a rosuvastatin calcium intermediate. The preparation method of the rosuvastatin calcium intermediate, namely, the compound shown as formula I in the description comprises the following steps: (1) a compound 5 shown as formula II in the description is generated from 4-fluorobenzaldehyde, methyl isobutyrylacetate and urea under the action of a catalyst; (2) a compound 6 shown as formula III in the description is generated from the compound 5 under the action of potassium persulfate as an oxidizing agent; (3) a compound 7 shown as formula IV in the description is generated from the compound 6, tosyl chloride and N-methyl methanesulfonamide under the action of a catalyst; (4) the target compound shown as the formula I is generated from the compound 7 under the action of a vitride solution as a reducing agent and crystallized with a crystallization solution, and a purified target compound is obtained. The preparation method of the rosuvastatin calcium intermediate has the advantages of low production cost, mild condition and simple and convenient operation.

Description

technical field [0001] The invention relates to the field of medicine synthesis, in particular to a preparation method of a rosuvastatin calcium intermediate. Background technique [0002] Rosuvastatin Calcium (Rosuvastatin Calcium), chemical name: bis-[E-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino ]-pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid]calcium salt, is a kind of statin hypolipidemic drug, belongs to hydroxymethylglutaryl coenzyme A ( HMG-CoA) reductase inhibitors. Rosuvastatin Calcium was purchased from Shionogi Pharmaceutical Co., Ltd., Japan. This product can significantly increase HDL-C while lowering LDC-C. Compared with other statins on the market, rosuvastatin calcium has better pharmacology in terms of HMG-COA reductase inhibition It has the advantages of low toxicity and side effects, and is known as "super statin". [0003] For the synthesis of rosuvastatin calcium, its important intermediate 4-(4-fluorophenyl)-6-isopropyl...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D239/42
CPCC07D239/42
Inventor 张立光龚逸奕丁荣敏
Owner SUZHOU HEALTH COLLEGE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap